Ngo, Van A.; Kim, Ilsoo; Allen, Toby W.; Noskov, Sergei Y.
Estimation of Potentials of Mean Force from Nonequilibrium Pulling Simulations Using Both Minh-Adib Estimator and Weighted Histogram Analysis Method
JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 12:1000-1010, MAR 2016

Nonequilibrium pulling simulations have been a useful approach for investigating a variety of physical and biological problems. The major target in the simulations is to reconstruct reliable potentials of mean force (PMFs) or unperturbed free-energy profiles for quantitatively addressing both equilibrium mechanistic properties and contributions from nonequilibrium processes. While several current nonequilibrium methods were shown to be accurate in computing free-energy profiles in systems with relatively simple dynamics, they have proved to be unsuitable in more complicated systems. To extend the applicability of nonequilibrium sampling, we demonstrate a novel method that combines Minh-Adib's bidirectional estimator with nonlinear WHAM equations to reconstruct and assess PMFs from relatively fast pulling trajectories. We test the method in a one-dimensional model system and in a system of an antibiotic gramicidin-A (gA) channel, which is considered a significant challenge for nonequilibrium sampling. We identify key parameters for efficiently performing pulling simulations to improve and ensure the convergence and accuracy of estimated PMFs. We show that a few pulling trajectories of a relatively fast pulling speed nu = 10 angstrom/ns can return a fair estimate of the PMF of a single potassium ion in gA.

DOI:10.1021/acs.jctc.5b01050

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